Paltusotine

Similar to the natural hormone somatostatin, paltusotine suppresses growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion. Paltusotine exerts its pharmacological activity via selective agonism (>4000-fold) at somatostatin receptor 2 (SSTR2) and exhibits little or no affinity for other SST receptor subtypes.

• PALSONIFY is indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. PALSONIFY is a somatostatin receptor agonist indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option ( 1 ).

• None.contraindicated

Take orally once daily with water on an empty stomach (at least 6 hours after a meal) and at least 1 hour before the next meal ( 2.1 ). Recommended initial dosage is 40 mg once daily. During initiation, PALSONIFY may be temporarily reduced to 20 mg once daily if needed, based on tolerability. Once adverse reactions have resolved, resume PALSONIFY 40 mg once daily ( 2.2 ). After 2 to 4 weeks, based on IGF-1 levels, titrate to 60 mg once daily ( 2.2 ). 2.1 Important Administration Instructions Take PALSONIFY orally once daily with water on an empty stomach, at least 6 hours after a meal (e.g., after overnight fasting) and at least 1 hour before the next meal [see Clinical Pharmacology ( 12.3 )] . 2.2 Recommended Dosage, Titration, and Monitoring The recommended initial dosage of PALSONIFY is 40 mg once daily. During initiation period, PALSONIFY may be temporarily reduced to 20 mg once daily if needed, based on tolerability [see Adverse Reactions ( 6.1 )] . Once adverse reactions have resolved, resume PALSONIFY 40 mg once daily. After 2 to 4 weeks on PALSONIFY 40 mg once daily, based on IGF-1 levels, titrate to a PALSONIFY dosage of 60 mg once daily. 2.3 Dosage Modifications for Drug Interactions Concomitant Use with Strong CYP3A4 Inducers Patients taking strong CYP3A4 inducers may require an increased dosage of PALSONIFY. Do not exceed three-fold the PALSONIFY dosage prior to concomitant use or 120 mg daily, whichever is less [see Drug Interactions ( 7.1 )] .

Cholelithiasis and its Complications: Monitor periodically. If complications of cholelithiasis occur, discontinue PALSONIFY and treat appropriately ( 5.1 ). Hyperglycemia and Hypoglycemia: Monitor glucose and adjust antidiabetic treatment as needed ( 5.2 ). Cardiovascular Abnormalities: Bradycardia or conduction abnormalities may occur. Dosage adjustments of concomitantly used drugs with bradycardia effects may be necessary ( 5.3 ). Thyroid Function Abnormalities: Hypothyroidism may occur. Assess thyroid function periodically ( 5.4 ). Steatorrhea and Malabsorption of Dietary Fats: New onset steatorrhea, stool discoloration, loose stools, abdominal bloating, and weight loss may occur. If new occurrence or worsening of these symptoms are reported, evaluate for potential pancreatic exocrine insufficiency ( 5.5 ). Vitamin B 12 Deficiency: Monitor vitamin B 12 levels during treatment if indicated ( 5.6 ). 5.1 Cholelithiasis and its Complications PALSONIFY may inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder stones or sludge. Cholelithiasis was reported in participants treated with PALSONIFY in clinical trials. Complications of cholelithiasis, such as acute cholecystitis and pancreatitis, have also been reported with the use of PALSONIFY [see Adverse Reactions ( 6.1 )] . Monitor patients periodically. If complications of cholelithiasis occur, discontinue PALSONIFY and treat appropriately.

The following clinically significant adverse reactions are described elsewhere in the labeling: Cholelithiasis and Complications of Cholelithiasis [see Warnings and Precautions ( 5.1 )] Hyperglycemia and Hypoglycemia [see Warnings and Precautions ( 5.2 )] Cardiovascular Abnormalities [see Warnings and Precautions ( 5.3 )] Thyroid Function Abnormalities [see Warnings and Precautions ( 5.4 )] Steatorrhea and Malabsorption of Dietary Fats [see Warnings and Precautions ( 5.5 )] Changes in Vitamin B 12 Levels [see Warnings and Precautions ( 5.6 )] Most common adverse reactions (≥5%) are diarrhea, abdominal pain, nausea, decreased appetite, sinus bradycardia, hyperglycemia, palpitations, and gastroenteritis ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Crinetics Pharmaceuticals, Inc. at toll-free phone 1-833-CRN-INFO or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of PALSONIFY was evaluated in adults with acromegaly in two randomized, double-blind, placebo-controlled Phase 3 studies. Study 1 was a 24-week, randomized, placebo-controlled study in 111 adults who were naive or previously treated on a somatostatin analog and biochemically uncontrolled at randomization.

8.1 Pregnancy Risk Summary The available data with PALSONIFY use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, no malformations were observed with oral administration of paltusotine to pregnant rats and rabbits during organogenesis at exposures 11 and 3 times the human exposure at the maximum recommended human dose (MRHD) of 60 mg once daily, respectively (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study in pregnant rats, paltusotine was administered orally at 25, 75, and 500 mg/kg/day during the period of organogenesis from gestation Day 7 to 17. The NOAEL for maternal and embryo-fetal developmental toxicity was 500 mg/kg/day, as no paltusotine-related effects were observed on any ovarian, uterine or litter parameters (approximately 11 times the MRHD based on AUC).

Metabolism

Paltusotine exhibited dose-proportional increases in exposures for doses ranging from 20 mg (lowest approved recommended dosage) to 120 mg (2 times the highest approved recommended dosage) in healthy participants. Apparent dose proportional increase was observed for mean steady-state trough concentrations up to 60 mg once daily in participants with acromegaly.

Overdose with somatostatin analogs may result in hyperglycemia or hypoglycemia, bradycardia, arrhythmia, diarrhea, vomiting, and other gastrointestinal symptoms. If overdose is suspected, initiate supportive treatment as dictated by patient's clinical status.

• Sep 25, 2025NDANDA219070Crinetics

1. 1Diarrhoea618%
2. 2Fatigue515%
3. 3Abdominal Discomfort412%
4. 4Headache412%
5. 5Abdominal Pain39.1%
6. 6Intentional Product Use Issue39.1%
7. 7Product Dose Omission Issue39.1%
8. 8Arthralgia26.1%
9. 9Asthenia26.1%
10. 10Compartment Syndrome26.1%
11. 11Influenza Like Illness26.1%
12. 12Intentional Dose Omission26.1%
13. 13Nausea26.1%
14. 14Pain26.1%
15. 15Abdominal Distension13.0%

The 7 most recently updated of 7 ClinicalTrials.gov registrations naming Paltusotine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Evaluate the Long-Term Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Advance)
  Active not recruiting · Phase 2 · Interventional · 43 enrolled · Crinetics Pharmaceuticals Inc.
  NCT04261712updated 2026-05-15
• A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (PATHFNDR-2)
  Active not recruiting · Phase 3 · Interventional · 111 enrolled · Crinetics Pharmaceuticals Inc.
  NCT05192382updated 2026-05-15
• A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly
  Active not recruiting · Phase 3 · Interventional · 58 enrolled · Crinetics Pharmaceuticals Inc.
  NCT04837040updated 2026-05-15
• Carcinoid Syndrome Efficacy Study Featuring an Oral Daily Paltusotine Regimen
  Recruiting · Phase 3 · Interventional · 141 enrolled · Crinetics Pharmaceuticals Inc.
  NCT07087054updated 2026-04-30
• Study to Evaluate the Safety, PK, and Dose Response of Paltusotine in Subjects With Carcinoid Syndrome
  Completed · Phase 2 · Interventional · 36 enrolled · Crinetics Pharmaceuticals Inc.
  NCT05361668updated 2026-03-19
• A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Evolve)
  Completed · Phase 2 · Interventional · 13 enrolled · Crinetics Pharmaceuticals Inc.
  NCT03792555updated 2025-03-17
• An Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Edge)
  Completed · Phase 2 · Interventional · 47 enrolled · Crinetics Pharmaceuticals Inc.
  NCT03789656updated 2025-02-17

Frequently asked questions

How does Paltusotine work?

Similar to the natural hormone somatostatin, paltusotine suppresses growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion. Paltusotine exerts its pharmacological activity via selective agonism (>4000-fold) at somatostatin receptor 2 (SSTR2) and exhibits little or no affinity for other SST receptor subtypes.

What is Paltusotine used for?

According to FDA labeling, Paltusotine carries indications including: PALSONIFY is indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. PALSONIFY is a somatostatin receptor agonist indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option ( 1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Paltusotine?

Paltusotine is classified as Somatostatin and analogues, Somatostatin Receptor Agonists, Decreased Growth Factor Activity, Decreased Growth Hormone Secretion.

What are the brand names for Paltusotine?

Paltusotine is marketed under brand names including Palsonify.

What are the contraindications for Paltusotine?

Paltusotine labeling lists contraindications including: None.. Always consult the full prescribing information and a clinician.