Drug Trials Snapshots: PALSONIFY
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the PALSONIFY Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
PALSONIFY (paltusotine)
(pal-SON-ih-figh)
Crinetics
Original approval date: September 25, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
PALSONIFY is a somatostatin receptor analog for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option.
How is this drug used?
PALSONIFY is available as an oral tablet and is taken once a day.
Who participated in the clinical trials?
The FDA approved PALSONIFY based on evidence from two clinical of 169 patients with acromegaly. The trials were conducted at 73 sites in 18 countries in Argentina, Belgium, Brazil, Bulgaria, China, France, Germany, Greece, Hungary, India, Israel, Italy, Peru, Poland, Serbia, Spain, United Kingdom (UK), and United States (US). Findings from both clinical trials established PALSONIFY’s safety and efficacy.
How were the trials designed?
PALSONIFY was evaluated in two randomized, double-blind, placebo-controlled trials. clinical trials in adult patients with acromegaly, of 24 weeks and of 36 weeks duration, respectively.
Both trials evaluated proportion of patients who achieved normalization of the insulin growth factor -1 (IGF-1) level at the end of trial(s) period.
How were the trials designed?
Trial 1 included 111 adult subjects with biochemically uncontrolled acromegaly at randomization. either treatment-naïve (n=46/111) or had no treatment within the previous 4 months prior to screening (n=36/111) (‘Not Medically Treated’ group) or were previously treated on a somatostatin receptor analog and then washed out of treatment during screening (n=29/111) (‘Washout’ group). The starting dose was 20 mg daily, followed by dose increase to 40 mg daily after 2 weeks. The dose could be titrated from 40 mg to a maximum dose of 60 mg based on IGF-1 value during the first 12 weeks of treatment. After Week 12, the PALSONIFY dose was maintained until the end of the randomized controlled period of the study (Week 24). The dose could be down titrated at any time during the study based on tolerability. The primary endpoint was the proportion of PALSONIFY subjects achieving biochemical control (defined as IGF-1 level ≤1.0×ULN) compared to placebo-treated subjects.
Trial 2 included 58 adult subjects with acromegaly who were biochemically controlled on other somatostatin analog therapy at randomization. The starting dose was 40 mg, and the dose could be titrated from 40 mg to a maximum of 60 mg based on IGF-1 value during the first 24 weeks of treatment. After Week 24, the PALSONIFY dose was maintained until the end of the randomized controlled period of the study (Week 36). The dose could be down titrated at any time during the study based on tolerability. The primary endpoint was the proportion of PALSONIFY subjects with biochemical response maintenance (i.e., IGF-1 ≤1.0×ULN) compared to placebo-treated subjects.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female participants were enrolled in the combined clinical trials used to evaluate the efficacy of PALSONIFY.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes how many participants by race were enrolled in the combined clinical trials used to evaluate the efficacy of PALSONIFY.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes how many participants by age were enrolled in the combined clinical trials used to evaluate the efficacy of PALSONIFY.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes how many participants by ethnicity were enrolled in the combined clinical trials used to evaluate the efficacy of PALSONIFY.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
What are the benefits of this drug?
In Trial 1, 56% of adult patients with acromegaly who were treated with PALSONIFY had IGF-1 < ULN after 24 weeks of treatment compared to 5% adult patients with acromegaly in the placebo arm.
In Trial 2, 83% of adult patients with acromegaly who were treated with PALSONIFY had IGF-1 < ULN after 36 weeks of treatment compared to 4% of adult patients with acromegaly in the placebo arm.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 1. Proportion of Participants Achieving Biochemical Control (IGF-1 Levels ≤1.0×ULN) at Week 24 (Trial 1) and at Week 36 (Trial 2) in Adults with Acromegaly
Primary Efficacy Endpoint | Placebo Responder n/N (%) | PALSONIFY Responder n/N (%) | Difference (95% CI) p-Value | |
|---|---|---|---|---|
| Trial 1 | Achieving biochemical response in IGF-1 (≤1.0×ULN) at Week 24 | 3/57 | 30/54 | 50.3 |
| Trial 2 | Achieving biochemical response in IGF-1 (≤1.0×ULN) at Week 36 | 1/28 | 25/30 | 79.8 |
Source: FDA Review
Abbreviations: CI, confidence interval; n = number of participants with event; N = total number of participants.; % = percentage: ULN = upper limit of normal.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: PALSONIFY worked similarly in males and females.
- Race: The number of patients of races other than White was small. Therefore, differences in how PALSONIFY worked among races could not be determined.
- Age: PALSONIFY worked similarly in patients regardless of age.
- Ethnicity: PALSONIFY worked similarly in Hispanic/Latino and Non-Hispanic/Latino.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 2. PALSONIFY versus Placebo Treatment Difference in Achieving Biochemical Control (IGF-1 Levels ≤1.0×ULN) at Week 24 (Trial 1) and at Week 36 (Trial 2) in Adults with Acromegaly by Sex, Age, Race and Ethnicity
Group | Subgroup | Trial 1 | Trial 2 |
|---|---|---|---|
Treatment Difference 95% C.I.* | Treatment Difference 95% C.I.* | ||
| Sex | Male | 48.6 (30.3, 66.8) | 80.5 (65.8, 94.0) |
| Female | 52.7 (34.9, 70.6) | 79.8 (63.4, 93.9) | |
| Age, years | <65 years | 48.3 (33.8, 62.7) | 80.7 (67.4, 93.3) |
| ≥65 years | 63.6 (39.4, 86.5) | 80.5 (64.9, 94.6) | |
| Race | Asian | 17.9 (-1.7, 37.0) | -- |
| White | 68.1 (51.7, 85.6) | 86.8 (77.4, 97.4) | |
| Other | 53.4 (29.8, 77.3) | 73.1 (45.0, 89.9) | |
| Ethnicity | Hispanic or Latino | 54.3 (32.5, 76.4) | 78.4 (59.8, 93.1) |
| Not Hispanic or Latino | 49.4 (32.8, 65.9) | 85.2 (74.8, 96.7) |
Source: Adapted from FDA Review
Abbreviations: CI, credible interval.
* Credible intervals include the relevance of outcomes from other subgroups.
Due to small number of participants Black or African American, Unknown and Multiple were combined with Other category of Race.
What are the possible side effects?
PALSONIFY may cause serious side effects, including:
- Gallbladder abnormalities
- High glucose levels or low glucose levels
- Heart rate decrease
- Thyroid function abnormalities
- Fatty stools and decreased absorption of dietary fats
- Low vitamin B12 levels in the blood
The most common side effects include diarrhea, abdominal pain, nausea, decreased appetite, sinus bradycardia, hyperglycemia, palpitation, and gastroenteritis.
What are the possible side effects (results of trials used to assess safety)?
Table 3. Adverse Reactions Occurring in ≥5% of PALSONIFY-Treated Participants and 5% Greater Incidence than Placebo-Treated Participants During the Randomized Controlled Period of Trial 1
Adverse Reaction | PALSONIFY N=54 n (%) | Placebo N=57 n (%) |
|---|---|---|
| Diarrhea | 18 (33) | 8 (14) |
| Abdominal pain a | 10 (19) | 3 (5) |
| Nausea | 5 (9) | 1 (2) |
| Sinus bradycardia | 4 (7) | 0 |
| Hyperglycemia b | 4 (7) | 1 (2) |
Source: FDA Review
Abbreviations: N = total number of patients in the group; n = number of patients with adverse reaction, % = percent of patients with adverse reaction
a Abdominal pain also includes abdominal discomfort.
b Hyperglycemia also includes impaired fasting glucose and diabetes mellitus.
Table 4. Adverse Reactions Occurring in ≥5% of PALSONIFY-Treated Participants and 5% Greater Incidence than Placebo-Treated Participants During the Randomized Controlled Period of Trial 2
Adverse Reaction | PALSONIFY N=30 n (%) | Placebo N=28 n (%) |
|---|---|---|
| Diarrhea | 7 (23) | 3 (11) |
| Nausea | 4 (13) | 1 (4) |
| Decreased appetite a | 3 (10) | 0 |
| Palpitations | 2 (7) | 0 |
| Gastroenteritis | 2 (7) | 0 |
Source: FDA Review
Abbreviations: N = total number of patients in the group; n = number of patients with adverse reaction, % = percent of patients with adverse reaction
a Decreased appetite also includes early satiety.
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The number of participants of races other than White was small. Therefore, the difference between races for the occurrence of side effects could not be determined.
- Age: The occurrence of side effects was similar in patients below and above 65 years of age.
Table 5. Overview of Adverse Events by Sex and Age During the Randomized Controlled Period of Trial 1
Characteristic | PALSONIFY N=54 n/Ns (%) | Placebo N=57 n/Ns (%) |
|---|---|---|
| Sex |
|
|
Female | 25/26 (96) | 31/33 (94) |
Male | 24/28 (86) | 17/24 (71) |
| Age group, years |
|
|
<65 | 42/47 (89) | 45/54 (83) |
≥65 | 7/7 (100) | 3/3 (100) |
Source: FDA Review
Abbreviations: N = total number of patients in the group; n = number of patients with adverse reaction, Ns = total number of patients for each specific subgroup assigned to the specific arm, % = percent of patients with adverse reaction
Table 6. Overview of Adverse Events by Sex and Age During the Randomized Controlled Period of Trial 2
Characteristic | PALSONIFY N=30 n/Ns (%) | Placebo N=28 n/Ns (%) |
|---|---|---|
| Sex |
|
|
Female | 13/15 (87) | 17/17 (100) |
Male | 11/15 (73) | 11/11 (100) |
| Age group, years |
|
|
<65 | 16/20 (80) | 22/22 (100) |
≥65 | 8/10 (80) | 6/6 (100) |
Source: FDA Review
Abbreviations: N = total number of patients in the group; n = number of patients with adverse reaction, Ns = total number of patients for each specific subgroup assigned to the specific arm, % = percent of patients with adverse reaction
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or "sugar pill" that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.